The material SRS-A (slow reacting substance of anaphylaxis) like histamine is released from cells of mammals during an allergic reaction. The SRS-A excreted by the cells contracts smooth muscle tissue producing such effects as asthmatic attacks. Thus there has been a great need for drugs which would specifically antagonize the effects of SRS-A released by the cells of man during an allergic response.
Conventional anti-allergic drugs such as anti-histamines, while effective in neutralizing the histamine produced during an allergic response, have been ineffective in neutralizing or antagonizing the effects of SRS-A. This has limited the usefulness of these antihistamines as anti-asthmatic agents. Therefore, it has long been desirable to develop drugs which will specifically antagonize the effects of SRS-A released during an allergic response.
In screening compounds for anti-SRS-A activity, natural SRS-A has been utilized. See Mielens, U.S. Pat. No. 4,174,402; Augstein et al., U.S. Pat. No. 3,882,148; Hitchcock, J. Pharmacol, Vol. 207, No. 6, page 630 (1978). A problem encountered with utilizing SRS-A obtained from natural sources in the many impurities which must be removed before the material can be used to determined the specific SRS-A antagonist effect of various compounds. SRS-A material from natural biological souces contains many difficult to separate impurities which interfere with the determination of whether a compound is specifically active against SRS-A. In some cases, a false positive may arise due to the activity of the compound to be tested against some component included within the natural SRS-A material and not SRS-A itself. To neutralize some of the contaminates such as acetyl choline and histamine present in biologically obtained SRS-A, various additives have been added to the naturally obtained SRS-A before testing. While these additives have to an extent neutralized these contaminates, residues of these contaminates may still be present which interfere with the assay. Furthermore, it has been desired to synthetically produce the active components in SRS-A to avoid such contaminates and produce a standard material. Such standard material would not contain contaminates which could interfere with the determination of the anti-SRS-A properties of a compound. Furthermore, a synthetically produced SRs-A active compound would avoid costly purification techniques not utilized in obtained natural SRS-A.
Recently the structure of SRS-A has been reported by Samuelsson et al., in Chemical and Engl News, June 11, 1979, p. 19 and in Science, 1979, Vol. 57, p. 19, who designates leukotriene C. having a structure as follows: ##STR1## where .DELTA.' indicates a trans configuration across the double bond and .DELTA. a cis configuration across the double bond.
On the other hand, Corey et al. in J. of Amer. Chemical society. 101:6748 (1979) has identified the material obtained by Samuelsson as a 5S,6R compound of the structure: ##STR2## where .DELTA. and .DELTA.' are as above.
While the compound obtained by Samuelsson has been found to have SRS-A activity, Samuelsson and Corey et al. in Biochem Biophys Research Com. Vol. 91, No. 4, 1979, believe that SRS-A has a different structure, having gluthione in place of cysteine.